Segal K R, Landt M, Klein S
Department of Pediatrics, Cornell University Medical College, New York, New York 10021, USA.
Diabetes. 1996 Jul;45(7):988-91. doi: 10.2337/diab.45.7.988.
Alterations in the production of or the sensitivity to leptin, the protein encoded by the ob gene, cause obesity and diabetes in rodents. We evaluated the isolated relationship between leptin and insulin sensitivity in lean and obese humans. Three groups of subjects who were carefully matched for either insulin sensitivity (determined by the modified intravenous glucose tolerance test and minimal model analysis) or adiposity (determined by hydrodensitometry) were studied: 1) lean insulin-sensitive men (percentage body fat, 15 +/- 1%); 2) lean insulin-resistant men (percentage body fat, 16 +/- 1%), matched on percentage body fat and fat mass with the lean insulin-sensitive group; and 3) obese insulin-resistant men (percentage body fat, 31 +/- 3), matched on insulin sensitivity with the lean insulin-resistant group. Basal plasma leptin concentrations were significantly lower in the lean insulin-sensitive than in the lean insulin-resistant men (1.90 +/- 0.4 vs. 4.35 +/- 1.21 ng/ml, P < 0.05) despite identical body composition. Plasma leptin in the obese men (9.27 +/- 1.4 ng/ml) was significantly higher than values in the two lean groups (P < 0.01). Marked alterations in plasma glucose and insulin concentrations induced by glucose and tolbutamide injection did not cause any change in plasma leptin levels. These results demonstrate that insulin resistance is associated with elevated plasma leptin levels independent of body fat mass. However, plasma insulin itself does not acutely regulate leptin production.
ob基因编码的蛋白质瘦素，其产生或敏感性的改变会导致啮齿动物肥胖和糖尿病。我们评估了瘦人和肥胖人群中瘦素与胰岛素敏感性之间的独立关系。研究了三组在胰岛素敏感性（通过改良的静脉葡萄糖耐量试验和最小模型分析确定）或肥胖程度（通过人体密度测定法确定）方面仔细匹配的受试者：1）瘦的胰岛素敏感男性（体脂百分比，15±1%）；2）瘦的胰岛素抵抗男性（体脂百分比，16±1%），在体脂百分比和脂肪量上与瘦的胰岛素敏感组匹配；3）肥胖的胰岛素抵抗男性（体脂百分比，31±3），在胰岛素敏感性上与瘦的胰岛素抵抗组匹配。尽管身体组成相同，但瘦的胰岛素敏感男性的基础血浆瘦素浓度显著低于瘦的胰岛素抵抗男性（1.90±0.4对4.35±1.21 ng/ml，P<0.05）。肥胖男性的血浆瘦素（9.27±1.4 ng/ml）显著高于两个瘦组的值（P<0.01）。葡萄糖和甲苯磺丁脲注射引起的血浆葡萄糖和胰岛素浓度的明显改变并未导致血浆瘦素水平发生任何变化。这些结果表明，胰岛素抵抗与血浆瘦素水平升高相关，且独立于体脂量。然而，血浆胰岛素本身并不会急性调节瘦素的产生。
